In medical infusion, the flow typically needs to be restricted to rather low rates, such as, for example, 1000 microliters per hour. Delivery of liquids at flow rates of up to a few milliliters per hour or less may be achieved by connecting a source of pressurized liquid to a capillary of small internal diameter. The rate of flow through the capillary has a well-defined relation to the length and internal diameter of the capillary, and to the difference in pressure between the capillary inlet and the capillary outlet. For any given pressure difference, the flow rate may be fixed at a desired value by choosing a capillary of suitable length and internal diameter.
A problem with capillaries of very small internal diameter (i.e., micro-capillaries) is that bubbles of gas in the liquid may have a serious impact on the pressure difference or pressure drop required to drive a given flow rate through the capillary and, in the worst case, bubbles may lead to an effective blocking of the capillary. This is due to the phenomenon of fragmentation of a larger bubble at the inlet of the capillary into a plurality of small bubbles within the capillary. The small bubbles are separated from each other by plugs of liquid and each small bubble requires a certain pressure difference between its ends to move along the capillary. That pressure difference is largely independent of bubble length. Bubble fragmentation at the inlet may fill the capillary with so many small bubbles that the pressure difference available for generating liquid flow is reduced or fully consumed by the sum of pressure drops needed to drive the small bubbles along the capillary. Therefore, flow through the capillary may be severely reduced or even stopped by bubble fragmentation.
Fused silica micro-capillaries with a constant internal diameter of 10 to 100 micrometers are widely used in the field of chemical analysis, in applications such as capillary electrophoresis and gas chromatography. Micro-capillary flow restrictors for use in medical infusion are made by cutting suitable lengths, for example a few centimeters each, off of fused silica micro-capillary stock. Other choices of material are also available, such as polymeric capillaries or micro-machined planar capillary structures.
Unfortunately, however, experience shows that the occurrence of bubble fragmentation in such known micro-capillary flow restrictors is not predictable. Out of 100 flow restrictors made, some 65 or so may have a very low tendency towards bubble fragmentation; whereas, others will fragment virtually any bubble that enters.
There is a lack of yield and a lack of predictability. Both are major obstacles in the industrial use of micro-capillary flow restrictors, for example in mass fabrication of medical infusion devices. See, for example, U.S. Pat. No. 7,431,052 for one approach to understanding and addressing the bubble fragmentation problem, the disclosure of which is incorporated herein by reference in its entirety. While achieving some success in addressing this issue through the use of a flow restrictor having an inlet with a particular contour that has less tendency towards bubble fragmentation, nonetheless bubble fragmentation still occurs. While the inlet contour is more predictable in its bubble fragmentation behavior and provides a higher yield of usable devices than conventional micro-capillary flow restrictors, problems still remain.